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Understanding the mechanism of cancer immune surveillance is crucial for precision medicine and effective immunotherapy. We report here that ZNF408, encoded by a gene linked to familial exudative vitreoretinopathy (FEVR) and autosomal recessive retinitis pigmentosa (RP), is physically associated with the SETD1A/COMPASS complex mediating histone H3 lysine 4 (H3K4) methylation in breast cancer cells. Integrative epigenomic and transcriptomic analyses reveal that ZNF408 and SETD1A share overlapped chromatin landscape and coordinately activate a cohort of genes, among which STING1 is critical in innate immune responses. ZNF408-SETD1A complex enhances STING1 expression and promotes STING-mediated anti-tumor immune responses both in vitro and in vivo. Importantly, ZNF408 expression is positively correlated with that of STING1 and negatively correlated with the histological grade of breast cancer. Our study uncovers a role for ZNF408 in cancer immune surveillance, supporting further investigations for therapeutic targeting of ZNF408-SETD1A-STING1 axis in breast carcinogenesis and other ZNF408-associated diseases including FEVR and RP.
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Plantarflexors provide propulsion during walking and receive input from both corticospinal and corticoreticulospinal tracts, which exhibit some frequency-specificity that allows potential differentiation of each tract's descending drive. Given that stroke may differentially affect each tract and impair the function of plantarflexors during walking; here, we examined this frequency-specificity and its relation to walking-specific measures during post-stroke walking. Fourteen individuals with chronic stroke walked on an instrumented treadmill at self-selected and fast walking speed (SSWS and FWS, respectively) while surface electromyography (sEMG) from soleus (SOL), lateral gastrocnemius (LG), and medial gastrocnemius (MG) and ground reaction forces (GRF) were collected. We calculated the intermuscular coherences (IMC; alpha, beta, and low-gamma bands between SOL-LG, SOL-MG, LG-MG) and propulsive impulse using sEMG and GRF, respectively. We examined the interlimb and intralimb IMC comparisons and their relationships with propulsive impulse and walking speed. Interlimb IMC comparisons revealed that beta LG-MG (SSWS) and low-gamma SOL-LG (FWS) IMCs were degraded on the paretic side. Intralimb IMC comparisons revealed that only alpha IMCs (both speeds) exhibited a statistically significant difference to random coherence. Further, alpha LG-MG IMC was positively correlated with propulsive impulse in the paretic limb (SSWS). Alpha and beta/low-gamma bands may have a differential functional role, which may be related to the frequency-specificity of the underlying descending drives. The persistence of alpha band in plantarflexors and its strong positive relationship with propulsive impulse suggests relative alteration of corticoreticulospinal tract after stroke. These findings imply the presence of frequency-specific descending drives to walking-specific muscles in chronic stroke.
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Selenium is among the important trace elements that influence the quality of meat. Although it has been established that the gut microbiota is closely associated with selenium metabolism, it has yet to be determined whether these microbes influence the accumulation of selenium in muscles. To identify gut microbiota that potentially influence the deposition of selenium in muscles, we compared the colonic microbial composition of pigs characterized by high and low contents of selenium in the longissimus dorsi muscle and accordingly detected a higher abundance of the bacterium Prevotella copri (P. copri) in pigs with a higher muscle selenium content. To verify the effect of P. copri, 16 pigs weighing approximately 61 kg were fed either a basal diet or a basal diet supplemented with P. copri (1.0 × 1010 CFU/kg feed) for 45 days. The results revealed significant increases in the contents of selenium and selenoprotein in the serum and longissimus dorsi muscle of fattening pigs fed the P. copri-supplemented diet. Moreover, supplementing the feed of pigs with P. copri was observed to promote significant improvement in the antioxidant capacity and quality of meat, including drip loss, pH, and meat color. In conclusion, our findings in this study indicate that P. copri has potential utility as a dietary supplement for improving the selenium status and meat quality in fattening pigs.
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The environment is an important factor affecting the composition and abundance of metabolites in O. sinensis, which indirectly determines its edible function and medicinal potential. This study integrated metabolomics and redundancy analysis (RDA) to analyze the metabolite profile characteristics and key environmental factors influencing O. sinensis in various production areas. A total of 700 differentially accumulated metabolites (DAMs) were identified, primarily comprising lipids, organic acids, and organoheterocyclic compounds. Results from hierarchical cluster analysis and KEGG indicated distinct accumulation patterns of these DAMs in O. sinensis from different regions, with enrichment in pathways such as tryptophan metabolism and glycerophospholipid metabolism. Environmental factors like annual mean precipitation, pH, temperature, and altitude were found to significantly influence metabolite composition, particularly lipids, organic acids, and nucleosides. Overall, this study highlights the impact of environmental factors on metabolite diversity in O. sinensis and sheds light on the evolutionary processes shaping its metabolic landscape.
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Background: The coronary artery calcium score (CACS) has been shown to be an independent predictor of cardiovascular events. The traditional coronary artery calcium scoring algorithm has been optimized for electrocardiogram (ECG)-gated images, which are acquired with specific settings and timing. Therefore, if the artificial intelligence-based coronary artery calcium score (AI-CACS) could be calculated from a chest low-dose computed tomography (LDCT) examination, it could be valuable in assessing the risk of coronary artery disease (CAD) in advance, and it could potentially reduce the occurrence of cardiovascular events in patients. This study aimed to assess the performance of an AI-CACS algorithm in non-gated chest scans with three different slice thicknesses (1, 3, and 5 mm). Methods: A total of 135 patients who underwent both LDCT of the chest and ECG-gated non-contrast enhanced cardiac CT were prospectively included in this study. The Agatston scores were automatically derived from chest CT images reconstructed at slice thicknesses of 1, 3, and 5 mm using the AI-CACS software. These scores were then compared to those obtained from the ECG-gated cardiac CT data using a conventional semi-automatic method that served as the reference. The correlations between the AI-CACS and electrocardiogram-gated coronary artery calcium score (ECG-CACS) were analyzed, and Bland-Altman plots were used to assess agreement. Risk stratification was based on the calculated CACS, and the concordance rate was determined. Results: A total of 112 patients were included in the final analysis. The correlations between the AI-CACS at three different thicknesses (1, 3, and 5 mm) and the ECG-CACS were 0.973, 0.941, and 0.834 (all P<0.01), respectively. The Bland-Altman plots showed mean differences in the AI-CACS for the three thicknesses of -6.5, 15.4, and 53.1, respectively. The risk category agreement for the three AI-CACS groups was 0.868, 0.772, and 0.412 (all P<0.01), respectively. While the concordance rates were 91%, 84.8%, and 62.5%, respectively. Conclusions: The AI-based algorithm successfully calculated the CACS from LDCT scans of the chest, demonstrating its utility in risk categorization. Furthermore, the CACS derived from images with a slice thickness of 1 mm was more accurate than those obtained from images with slice thicknesses of 3 and 5 mm.
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A series of novel quinazoline-derived EGFR/HER-2 dual-target inhibitors were designed and synthesized by heterocyclic-containing tail approach. The inhibitory activities against four human epidermal growth factor receptor (HER) isozymes (EGFR, HER-2, HER-3 and HER-4) of all new compounds so designed were investigated in vitro. Compound 12k was found to be the most effective and rather selective dual-target inhibitor of EGFR and HER-2 with inhibitory constant (IC50) values of 6.15 and 9.78 nM, respectively, which was more potent than the clinical used agent Lapatinib (IC50 = 8.41 and 9.41 nM). Meanwhile, almost all compounds showed excellent antiproliferative activities against four cancer cell models (A549, NCI-H1975, SK-BR-3 and MCF-7) and low damage to healthy cells. Among them, compound 12k also exhibited the most prominent antitumor activity. Moreover, the hit compound 12k could bind to EGFR and HER-2 stably in molecular docking and dynamics studies. The following wound healing assay revealed that compound 12k could inhibit the migration of SK-BR-3 cells. Further studies found that compound 12k could arrest cell cycle in the G0/G1 phase and induce SK-BR-3 cells apoptosis. Notably, compound 12k could effectively inhibit breast cancer growth with little toxicity in the SK-BR-3 cell xenograft model. Taken together, in vitro and in vivo results disclosed that compound 12k had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth.
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Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Receptores ErbB , Inhibidores de Proteínas Quinasas , Quinazolinas , Receptor ErbB-2 , Humanos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Quinazolinas/farmacología , Quinazolinas/química , Quinazolinas/síntesis química , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Animales , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Ratones , Línea Celular Tumoral , Simulación del Acoplamiento Molecular , Apoptosis/efectos de los fármacos , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/síntesis química , FemeninoRESUMEN
This study aimed to evaluate the effects of Clostridium butyricum (C. butyricum) on the prevention of the diarrhea rates and growth performances of weaned piglets induced by Escherichia coli K88 (E. coli K88). Twenty-four weaned piglets (6.92 ± 0.11 kg) were randomly assigned to one of three treatment groups for a period of 21 days. Each group consisted of eight pigs, with each pig being housed in an individual pen. Group I received the control diet along with normal saline, Group II received the control diet along with E. coli K88, and Group III received the control diet supplemented with 5 × 108 CFU/kg of C. butyricum and E. coli K88. We examined alterations in rectal microbiota and metabolites, analyzed the incidence of diarrhea, and investigated the interactions between microbiota and metabolites through the application of Illumina MiSeq sequencing and liquid chromatography-mass spectrometry. The results showed that, from days 14 to 21, the diarrhea incidence in Group III decreased significantly by 83.29% compared to Group II (p < 0.05). Over the entire experimental duration, the average daily feed intake of Group III decreased significantly by 11.13% compared to Group I (p < 0.05), while the diarrhea incidence in Group III decreased by 71.46% compared to Group II (p < 0.05). The predominant microbial flora in the rectum consisted of Firmicutes (57.32%), Bacteroidetes (41.03%), and Proteobacteria (0.66%). Administering E. coli K88 orally can elevate the relative abundance of Megasphaera (p < 0.05). Conversely, the supplementation of C. butyricum in the diet reduced the relative abundance of Megasphaera (p < 0.05), while increasing the relative abundance of unclassified_f_Lachnospiraceae (p < 0.05). Rectal metabolomics analysis revealed that supplementing C. butyricum in the feed significantly altered the amino acids and fatty acids of the piglets infected with E. coli K88 (p < 0.05). The correlation analysis showed that the occurrence of diarrhea was inversely related to adipic acid (p < 0.05) and positively associated with (5-hydroxyindol-3-YL) acetic acid and L-aspartic acid (p < 0.05). Prevotella_1 exhibited a negative correlation with octadecanoic acid (p < 0.05). Prevotellaceae_UCG-005 showed a negative correlation with (5-hydroxyindol-3-YL) acetic acid (p < 0.05). The findings from this research study aid in probiotic development and the enhancement of healthy growth in weaned piglets.
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The meat production traits of pigs are influenced by the expression regulation of multiple gene types, including mRNAs, miRNAs, and lncRNAs. To study the differences in meat production traits at the transcriptional level among individuals with different growth rates, the longissimus dorsi samples from eight Duroc × Bama Xiang F2 crossbred pigs with a fast growth rate (high gTroup) or a slow growth rate (low group) were selected to perform whole transcriptome sequencing and ceRNA regulatory network construction. This study first analyzed the differences in physiological and biochemical indicators, muscle histological characteristics, and muscle fiber types. A total of 248 mRNAs, 25 miRNAs, and 432 lncRNAs were identified as differentially expressed by whole transcriptome sequencing. Key genes that may influence meat production traits include MTMR14, PPP1R3A, PYGM, PGAM2, MYH1, and MYH7. The ceRNA regulatory network map showed that ENSSSCG00000042061-ssc-mir-208b-MYH7, ENSSSCG00000042223-ssc-mir-146a-MTMR14, ENSSSCG00000045539-ssc-mir-9-3-MYH1, and ENSSSCG00000047852-ssc-mir-103-1-PPP1R3A may be the key factors affecting meat production traits through their regulatory relationships. This study provides valuable insights into the molecular mechanisms underlying porcine muscle development and can aid in improving meat production traits.
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Artificial regulation of plant rhizosphere microbial communities through the synthesis of microbial communities is one of the effective ways to improve plant stress resistance. However, the process of synthesizing stress resistant microbial communities with excellent performance is complex, time-consuming, and costly. To address this issue, we proposed a novel strategy for preparing functional microbial communities. We isolated a cultivable cold tolerant bacterial community (PRCBC) from the rhizosphere of peas, and studied its effectiveness in assisting rice to resist stress. The results indicate that PRCBC can not only improve the ability of rice to resist cold stress, but also promote the increase of rice yield after cold stress relieved. This is partly because PRCBC increases the nitrogen content in the rhizosphere soil, and promotes rice's absorption of nitrogen elements, thereby promoting rice growth and enhancing its ability to resist osmotic stress. More importantly, the application of PRCBC drives the succession of rice rhizosphere microbial communities, and promotes the succession of rice rhizosphere microbial communities towards stress resistance. Surprisingly, PRCBC drives the succession of rice rhizosphere microbial communities towards a composition similar to PRCBC. This provides a feasible novel method for artificially and directionally driving microbial succession. In summary, we not only proposed a novel and efficient strategy for preparing stress resistant microbial communities to promote plant stress resistance, but also unexpectedly discovered a possible directionally driving method for soil microbial community succession.
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Microbiota , Oryza , Rizosfera , Microbiología del Suelo , Microbiota/fisiología , Oryza/fisiología , Oryza/microbiología , Frío , Respuesta al Choque por Frío/fisiología , Bacterias/metabolismoRESUMEN
For the first time, the dominant magnetoelectric activity of ZIF-67-derived carbonaceous microparticles embedded with Co nanoparticles and distinctive magnetothermal effect of MIL-88B-derived Fe3O4 nanocubes decorated on carbonaceous microrods, respectively, were explored to be controlled by the structure of the MOF-derived electrically conductive carbonaceous matrix and metal nanoparticles.
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Constructing highly efficient electrocatalysts is vital to enhance oxygen evolution reaction (OER) performance at industrially relevant current densities. Herein, three-phase coupled Ni3S2/r-NiS/h-NiS composites are grown in situ on Ni foam (NNSN/NF) via a one-step solvothermal approach. The as-prepared composites need overpotentials of only 377 mV, 451 mV and 476 mV at 1000 mA cm-2 for the OER in alkaline freshwater, simulated seawater and seawater, respectively. In addition, the optimized catalyst exhibited long-term durability at 300 mA cm-2. Our work clarifies designing and preparing cost-effective Ni-based sulfide electrocatalysts for the OER in alkaline freshwater/simulated seawater/seawater under industrially relevant current densities.
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Sepsis-related brain injury (SRBI) refers to brain dysfunction and structural damage caused by sepsis, which is characterized by inflammation, oxidative stress, and destruction of the blood-brain barrier. Pioglitazone is a PPAR-γ agonist in which PPAR-γ acts as an inflammatory modulator, determining the relationship between PPAR-γ and SRBI and inflammatory state is critical for the disease. This study aimed to construct a drug-target-disease network for SRBI and Pioglitazone based on network pharmacology, and to investigate the therapeutic effect and potential mechanism of Pioglitazone in SRBI induced by lipopolysaccharide (LPS) in rats through transcriptomics. To establish a rat Model of SRBI by intraperitoneal injection of LPS (10 mg/kg): SD rats were divided into Control, Model (LPS), Pioglitazone, (LPS + Pioglitazone) and GW9662 group (LPS+GW9662). The effects and potential mechanisms of Pioglitazone in the treatment of SRBI were studied using biochemical indexes, pathological changes and transcriptome-sequencing (RNA-seq). RNA-seq results showed 620 DEGs between the Model and the Pioglitazone groups. Enrichment analysis involved multiple inflammatory response processes and chemokine receptor binding functions. TLR4 and CXCL10 in the Toll signaling pathway may play an important role in SRBI as important targets. Pioglitazone may ameliorate SRBI through the PPAR-γ/TLR4/CXCL10 pathway.
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BACKGROUND: Up to 80 % of chemotherapeutic drugs induce myelosuppression in patients. Chemotherapy not only impairs of hematopoietic stem cells (HSCs) but also damages bone marrow niches (vascular and endosteal). Current treatments for myelosuppression overlook these chemotherapy-induced damages to bone marrow niches and the critical role of niche restoration on hematopoietic regeneration. Ginsenoside protopanaxatriol (PPT) protects vascular endothelium from injury, while icariin (ICA) promotes osteogenic differentiation. The combination of PPT and ICA aims to restore damaged vascular and endosteal niches, thus rejuvenating HSCs for treating myelosuppression. PURPOSE: This study aims to develop effective, bone marrow niche-directed PPT/ICA therapies for treating chemotherapy-induced myelosuppression. METHODS: 3D cell spheroids were used to investigate the effects of PPT/ICA on cell-cell interactions in vascular niches, osteogenesis, and extracellular matrix (ECM) secretion in endosteal niches. In vitro mimic niche models were designed to access the drug combination's efficacy in rejuvenating and mobilizing in HSCs within bone marrow niches. The delivery capability of PPT/ICA to key niche cell types (mesenchymal stromal cells (MSCs), endothelial cells (ECs), and osteoblasts (OBs)) via nanocarriers has been determined. DSS6 peptide-modified nanoparticles (DSS6-NPs) were prepared for specific co-delivery of PPT/ICA into key niche cell populations in vivo. RESULTS: PPT can prevent vascular niche injury by restoring vascular EC cell-cell adhesion and the intercellular interactions between ECs and MSCs in 5-fluorouracil (5-FU)-damaged cell spheroids. ICA repaired 5-FU-damaged endosteal niches by promoting osteogenesis and ECM secretion. The combination of PPT and ICA restores key HSC niche factor gene expressions, normalizing HSC differentiation and mobilization. The in vitro cellular uptake efficiency of nanocarriers in a mimic niche is positively correlated with their in vivo delivery into bone marrow niche cells. DSS6-NPs greatly enhance the delivery of PPT/ICA into MSCs and OBs within bone marrow niches. Co-loading of PPT/ICA into DSS6-NPs effectively repairs damaged bone marrow niches and promotes HSC rejuvenation in vivo. CONCLUSION: The combination of PPT and ICA effectively prevents injury to the vascular and endosteal niches, thereby promoting hematopoietic regeneration in the bone marrow. This study provides novel niche-directed PPT/ICA therapies for managing chemotherapy-induced myelosuppression.
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BACKGROUND: The expression of CYP19A1 has implications for the prognosis of female bladder cancer. However, this study aimed to explore the association between single nucleotide polymorphisms (SNPs) in CYP19A1 and bladder cancer risk, as no prior research has addressed this association. RESEARCH DESIGN AND METHODS: We selected and genotyped five CYP19A1 SNPs (rs4646, rs6493487, rs1062033, rs17601876, and rs3751599) in 217 patients and 550 controls using the Agena MassARRAY system. Logistic regression analysis was employed to calculate the odds ratio (OR) and 95% confidence intervals (CIs). Bioinformatics predicted SNP functions and CYP19A1 involving pathways. RESULTS: Our study revealed a significant association between bladder cancer risk and four SNPs (rs4646 (AC vs. CC: OR = 1.71, FDR-p = 0.005), rs6493487 (G vs. A: OR = 0.68, FDR-p = 0.011), rs1062033 (G vs. C: OR = 0.36, FDR-p < 0.001), and rs17601876 (GA vs. GG: OR = 1.66, FDR-p = 0.008)) in CYP19A1. The three SNPs (rs4646, rs1062033, and rs17601876) were significantly correlated with CYP19A1 expression levels in normal whole blood (p < 0.05). Moreover, CYP19A1 was found to primarily participate in the steroid hormone biosynthesis and metabolic pathways. CONCLUSIONS: Consequently, CYP19A1 gene polymorphisms may play a crucial role in the genetic susceptibility to bladder cancer.
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Aromatasa , Pueblo Asiatico , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Femenino , Persona de Mediana Edad , Aromatasa/genética , Estudios de Casos y Controles , Masculino , Anciano , Pueblo Asiatico/genética , Genotipo , China/epidemiología , Oportunidad Relativa , Estudios de Asociación Genética , Factores de Riesgo , Alelos , Frecuencia de los Genes , Pueblos del Este de AsiaRESUMEN
Background: Shame-proneness, particularly in adolescence, is a critical psychological construct linked to aggressive behavior. This study addresses the gap in understanding the specific mechanisms of this relationship within the cultural context of Chinese adolescents. Aim: The study aims to explore the mediating roles of hostility and externalization of blame in the connection between shame-proneness and aggression among Chinese adolescents. Methods: A comprehensive sample of 1489 Chinese adolescents participated in the study. They completed the Test of Self-Conscious Affect for Adolescents to assess shame-proneness and an aggression questionnaire to measure aggressive behaviors. The study utilized network analysis and mediational analysis, to unravel the complex interactions between shame-proneness, externalization of blame, hostility, anger, and aggression. Results: The results identified two distinct pathways linking shame-proneness to aggression: one mediated by hostility and the other by externalization of blame. The pathway via hostility was particularly pronounced, marking it as a central node in the shame-aggression relationship. Interestingly, the study also revealed a direct, though less pronounced, inhibitory effect of shame-proneness on aggression, indicating a dualistic role of shame in adolescent behavior. These findings were consistent across different demographic subgroups, suggesting a generalizable pattern in the studied population. Conclusion: The dual nature of shame-proneness, as both an inhibitor and a facilitator of aggression, underscores the need for culturally sensitive approaches in psychological interventions and future research. The central role of hostility in this relationship points to potential targets for therapeutic interventions aimed at mitigating aggression in adolescents.
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Microbiota has been closely related to human beings, whose role in tumor development has also been widely investigated. However, previous studies have mainly focused on the gut, oral, and/or skin microbiota. In recent years, the study of intratumoral microbiota has become a hot topic in tumor-concerning studies. Intratumoral microbiota plays an important role in the occurrence, development, and response to treatment of malignant tumors. In fact, increasing evidence has suggested that intratumoral microbiota is associated with malignant tumors in various ways, such as promoting the tumor development and affecting the efficacy of chemotherapy and immunotherapy. In this review, the impact of intratumoral microbiota on the immune microenvironment of malignant tumors has been analyzed, as well as its role in tumor immunotherapy, with the hope that it may contribute to the development of diagnostic tools and treatments for related tumors in the future.
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Inmunoterapia , Microbiota , Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/microbiología , Inmunoterapia/métodos , Microbiota/inmunología , AnimalesRESUMEN
Abnormal immune and inflammatory responses are considered to contribute to schizophrenia (SZ). The neutrophil/lymphocyte ratio (NLR) is an inexpensive and reproducible marker of systemic inflammatory responses. Accumulating studies have demonstrated that NLR values are increased in SZ compared to healthy controls and closely related to clinical symptoms in antipsychotic-naïve first-episode SZ (ANFES) patients. However, to our knowledge, only one study has examined NLR in relation to neurocognition in 27 first-episode psychosis patients and 27 controls. This study aimed to examine the relationship of NLR values with cognitive performances in ANFES patients with a larger sample size. Whole blood cell counts were measured in ninety-seven ANFES patients and fifty-six control subjects. The neurocognitive functions of all subjects were measured by the repeatable battery for the assessment of neuropsychological status (RBANS). ANFES patients performed worse on cognition and had increased NLR values relative to healthy controls. In addition, increased NLR was negatively associated with cognitive functions in ANFES patients. Lymphocyte count was positively correlated with cognitive functions in patients. These findings suggest that the abnormal immune and inflammation system indicated by NLR may be involved in the cognitive functions in ANFES patients.
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The treatment efficiency of acidic phenol-containing wastewater is hindered by the absence of efficient acid-resistant phenol-degrading bacteria, and the acid-resistant mechanism of such bacteria remains poorly studied. In this study, the acid-resistant strain Hly3 was used as a research model to investigate its ability to degrade phenol and its underlying mechanism of acid resistance. Strain Hly3 exhibited robust acid resistance, capable of surviving in extremely acidic environments (pH 3) and degrading 1700 mg L-1 phenol in 72 h. Through the physiological response analysis of strain Hly3 to pH, the results indicated: firstly, the strain could reduce the relative permeability of the cell membrane and increase EPS secretion to prevent H+ from entering the cell (shielding effect); secondly, the strain could accumulate more buffering substances to neutralize the intracellular H+ (neutralization effect); thirdly, the strain could expel H+ from the cell by enhancing H+-ATPase activity (pumping effect); finally, the strain produced more active scavengers to reduce the toxicity of acid stress on cells (antioxidant effect). Subsequently, combining liquid chromatography-mass spectrometry (LC-MS) technology with exogenous addition experiments, it was verified that the acid resistance mechanism of microorganisms is achieved through the activation of acid-resistant response systems by glutamine, thereby enhancing functions such as shielding, neutralization, efflux, and antioxidation. This study elucidated the acid resistance mechanism of Acinetobacter pittii, providing a theoretical basis and guidance for the treatment of acidic phenol-containing wastewater.
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Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.
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Anemia , Eritropoyesis , Receptor Toll-Like 8 , Humanos , Eritropoyesis/genética , Receptor Toll-Like 8/metabolismo , Receptor Toll-Like 8/genética , Femenino , Anemia/genética , Masculino , Linaje , Eritropoyetina/metabolismo , Eritropoyetina/genética , Adulto , Transducción de Señal , Mutación , Células Eritroides/metabolismo , Animales , Células Precursoras Eritroides/metabolismoRESUMEN
Mixed culture of microorganisms is an effective method to remove high concentration of phenol in wastewater. At present, it is still a challenge for microorganisms to remove high-concentration phenol from wastewater. In this study, a phenol-degrading consortium was isolated, which could rapidly degrade 1800 mg/L phenol within 30 h, and the highest phenol degradation concentration was 2000 mg/L. Further exploration of how microbial consortium cooperates to promote phenol biodegradation was studied: the core bacteria of the microbial consortium was relatively stable during phenol degradation; the bacteria could improve the adaptability to environment and metabolic ability of phenol, by producing more surfactants and betaine, thereby improving the degradation rate. The determination coefficient (R2) in the machine learning model showed that the back propagation artificial neural network (BP-ANN) can predict the biodegradation of phenol under different conditions, saving time and economic costs. This study explains how microbial consortium cooperates to degrade phenol from the aspects of microbial consortium composition and metabolic analysis, which provides a theoretical basis for mixed culture microorganisms to degrade pollutants.